key: cord-0941806-y1vjka66
authors: Shakoor, Muhammad Tariq; Birkenbach, Mark P.; Lynch, Matthew
title: ANCA-Associated Vasculitis Following the Pfizer-BioNTech COVID-19 Vaccine
date: 2021-07-17
journal: Am J Kidney Dis
DOI: 10.1053/j.ajkd.2021.06.016
sha: cd15c19d2bb1df0e1a30a8be708bddd780268bef
doc_id: 941806
cord_uid: y1vjka66

SARS-CoV-2 continues to spread around the world. As of June 28(th) 2021, there are approximately 181 million confirmed cases and more than 3.9 million deaths across the globe. The colossal impact of COVID19 is driving the biggest vaccination campaign in human history. All three vaccines (Pfizer-BioNTech, Moderna and J&J) authorized for emergency use by FDA have been thoroughly studied and found to be safe and effective in preventing severe COVID-19 cases. While short-term side effects of COVID-19 vaccine resemble those of other vaccines, long-term side effects remain unknown. Rare side effects continue to surface as millions of people receive COVID19 vaccines around the world as compared with the thousands enrolled in the clinical trials. We report a case of new onset renal limited ANCA-associated (AAV) vasculitis in a 78 year old woman with previously normal kidney function after receiving the Pfizer-BioNTech COVID-19 vaccine. The patient developed AKI with proteinuria and microscopic hematuria with many dysmorphic red blood cells in the urine. Anti-myeloperoxidase (MPO) antibody titer was elevated. Kidney biopsy showed pauci-immune crescentic necrotizing glomerulonephritis. Kidney function improved after treatment with steroids and rituximab. Our patient had normal routine lab work before the vaccination. Although this case cannot demonstrate a causal relationship between COVID19 vaccination and AAV, ongoing surveillance for similar complications would be prudent as worldwide vaccination efforts continue.

As of June 2021, a total of 33 million cases of coronavirus disease 2019 (COVID19), with more than a half-million COVID19 related deaths, have been reported in the United States alone. 1 The United States Food and Drug Administration (FDA) issued an emergency use authorization (EUA) of two COVID19 vaccines (Pfizer-BioNTech and Moderna) in December 2020 and a third (Janssen/ J&J) in February 2021. Large clinical trials showed that the vaccines are safe and effective. Common adverse events include mild to moderate tenderness at the injection site, fever, fatigue, body aches, and headaches. 2, 3 Reports of anaphylaxis to COVID19 vaccines also started to surface soon after the COVID19 vaccination campaign began, 4,5 but long-term sequalae of the vaccines remain unknown.

Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. 6 While there are many case reports describing a temporal association between influenza vaccination and new onset/relapse of AAAV, [7] [8] [9] [10] [11] there are few reports of this occurring after receiving the COVID19 vaccine. 15 We report a case of new onset renal limited antimyeloperoxidase (MPO)-AAV following COVID19 vaccination.

A 78-year-old female with a past medical history of type II diabetes mellitus, hypertension and paroxysmal atrial fibrillation, received her first dose of the Pfizer-BioNTech COVID19 vaccine on 2/1/2021, after which she developed nausea, vomiting and diarrhea. Routine laboratory assessments obtained 2 weeks after vaccination were notable for a serum creatinine of 1.3 J o u r n a l P r e -p r o o f mg/dl and urinalysis with 3+ blood, 99 RBCs/HPF, 7WBC/HPF and 100 mg/dl protein (Table   1 ). Routine laboratory assessments obtained a few weeks prior to vaccination were notable for serum creatinine 0.77 mg/dl and urinalysis with absent hematuria and proteinuria. Her symptoms improved spontaneously, and she received the second dose of the Pfizer-BioNTech COVID19 vaccine shot on 2/23/2021. After the second dose, she once again noted symptoms of nausea, vomiting and diarrhea, as well as new onset lethargy. At this time, laboratory assessments were notable for serum creatinine 3.54 mg/dl and urinalysis with 3+ blood, 96

RBCs/HPF, 7WBC/HPF and 100 mg/dl protein (Table 1) . The patient had no documented history of COVID19.

She was referred to emergency department, where CT of the abdomen and pelvis showed no acute abnormality. She was started on intravenous crystalloid, without improvement in serum creatinine, prompting nephrology consult. A manual urine microscopy revealed 1-2 granular casts/HPF, few renal tubular epithelial cells, too numerous to count red blood cells (>10% dysmorphic) and few white blood cells. Random urine albumin to creatinine ratio was 2.05 gram/gram. She was found to have an elevated titer of anti-MPO antibody (titer 1.1, normal <0.2).

Complement levels, and other serologic tests were The patient was started on intravenous methylprednisolone for three days, which was then prednisone 1 mg/kg daily. Kidney biopsy revealed crescentic necrotizing GN with moderate interstitial inflammation on light microscopy Vaccines reduce the risk of many life-threatening diseases by enhancing our body's natural immune response. As the body builds up the immunity, minor symptoms, including fever, body aches, headaches and injection site soreness, are expected. Recently, the FDA expeditiously approved three different COVID19 vaccines. Whether autoimmune diseases can be triggered after vaccination remains disputed among experts. 12 Here, we describe a case of new onset renal limited MPO-AAV after COVID19 vaccination. Millions of people are being vaccinated around the world, 5 and thus it is conceivable that people may develop other diseases temporally associated with vaccination but which are unrelated to the vaccine itself. Our patient had normal routine laboratory parameters before the vaccination, raising the index of suspicion for the observed correlation.

Although there is some dispute on the relationship between vaccination and AAV recurrence in patients with pre-existing autoimmune disease after influenza vaccination, many of the studies might have been underpowered to detect this very rare but significant side effect. 13 The temporal relationship could be explained by theoretical mechanisms, like molecular mimicry, polyclonal activation or transient systemic proinflammatory cytokines response, which can provoke autoimmune diseases in genetically predisposed individuals. 8 Observational studies have suggested a connection between different infections and development of vasculititides, although no direct proof exists. 14 Interestingly, Jeffs et al. noted increased ANCA production in response to viral RNA based influenza and rabies vaccines. 8 

Authors also noted substantially reduced ANCA response to RNA vaccine once vaccine was treated with RNAse. 8 

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Reports of Anaphylaxis After Receipt of mRNA COVID-19

Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID-19 Vaccine -United States

ANCA Glomerulonephritis and Vasculitis

ANCA-associated vasculitis following influenza vaccination: causal association or mere coincidence?

Viral RNA in the influenza vaccine may have contributed to the development of ANCA-associated vasculitis in a patient following immunisation

Antineutrophil cytoplasmic antibody vasculitis associated with influenza vaccination

MPO-ANCA associated vasculitis with mononeuritis multiplex following influenza vaccination

Vasculitis Following Influenza Vaccination: A Review of the Literature

Randomized trial investigating the safety and efficacy of influenza vaccination in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton)

Newly Diagnosed Glomerulonephritis During COVID-19 Infection Undergoing Immunosuppression Therapy, a Case Report

ANCA-associated vasculitis after COVID-19

Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19